Method for preparing a composition containing at least one internal dehydration product for a hydrogenated sugar

ABSTRACT

The subject of the present invention is a novel method for preparing a composition of internal dehydration product of a hydrogenated sugar, comprising:  
     a) a step of distilling a medium containing the said internal dehydration product in order to obtain a distillate enriched with this product,  
     b) optionally, at least one subsequent step of purifying the distillate thus obtained,  
     c) a subsequent step of bringing the distillate obtained during step a), and then optionally subjected to step b), into contact with an agent capable of improving the stability of the internal dehydration product predominantly contained in the distillate, the said agent not being in gaseous form,  
     d) optionally, a subsequent step of shaping the resulting composition of internal dehydration product of a hydrogenated sugar.  
     This method makes it possible in particular to obtain a stable isosorbide composition, characterized by its purity and/or its content of certain stabilizing or nonstabilizing species.

[0001] The present invention concerns a novel method for preparing acomposition containing at least one internal dehydration product of ahydrogenated sugar.

[0002] It also relates to the use of the composition thus prepared inthe preparation of polymeric or nonpolymeric, biodegradable ornonbiodegradable products or mixtures intended in particular for thechemical, pharmaceutical, cosmetic or food industries.

[0003] Finally, the present invention also concerns, as a novel productwhich can be obtained according to the said method, a composition of thetype in question having specific characteristics, especially in terms ofstability, purity and/or content of certain stabilizing ornonstabilizing species.

[0004] The expression “hydrogenated sugar” for the purposes of thepresent invention is understood to mean in particular:

[0005] hexitols such as, for example, sorbitol, mannitol, iditol andgalactitol,

[0006] pentitols such as, for example, arabitol, ribitol and xylitol,and

[0007] tetritols such as, for example, erythritol.

[0008] The expression “internal dehydration product” is understood tomean any product resulting, in any manner, in one or more steps, fromthe removal of one or more molecules of water from the original internalstructure of a hydrogenated sugar such as those mentioned above.

[0009] This may advantageously be internal dehydration products ofhexitols, in particular of dianhydrohexitols or “isohexides” such asisosorbide (1,4-3,6-dianhydrosorbitol), isomannide(1,4-3,6-dianhydromannitol) or isoidide (1,4-3,6-dianhydroiditol).

[0010] Among these doubly dehydrated hydrogenated sugars, isosorbide iscurrently the one for which the largest number of industrialapplications is being developed, or at the very least envisaged. Theyrelate to in particular:

[0011] the preparation of isosorbide 2-nitrate, 5-nitrate or2,5-dinitrate, which are useful in the therapeutic treatment ofdiseases, in particular cardiac and/or vascular diseases—as described inU.S. Pat. No. 4,371,703;

[0012] the preparation of alkylated, in particular dimethylated,derivatives of isosorbide, which are useful in particular as solvents inthe context of the preparation of pharmaceutical or cosmeticcompositions (U.S. Pat. No. 4,082,881), or even as active ingredients incompositions for oral hygiene (EP patent 315 334);

[0013] the preparation of isosorbide derivatives which can be used indetergent compositions for fuels (EP patent 1 106 616),

[0014] the preparation of alkylated or alkenylated derivatives which canbe used as plasticizers for polymers, adhesives or inks (patent WO99/450060), the preparation of specific biphosphites which can be usedas stabilizing agents for polymers or lubricants (FR patent 2 757 517),

[0015] the preparation of articles based on polyvinyl alcohol (U.S. Pat.No. 4,529,666), polyurethanes (U.S. Pat. No. 4,383,051), or polyestersalso containing monomer units of the “terephthaloyl” type (patents U.S.Pat. No. 3,233,752 and U.S. Pat. No. 6,025,061);

[0016] the preparation of polycondensates as described in the article byH. R. KRICHELDORF published in the Journal of MacromolecularScience—REV. MACROMOL. CHEM. PHYS., C 37 (4), 599-631 (1997),

[0017] the preparation of biodegradable polycondensates (patent WO 99/45054);

[0018] the preparation of aqueous lacquers (U.S. Pat. No. 4,418,174) orof compositions with surface covering and/or colouring action (U.S. Pat.No. 5,766,679).

[0019] For the majority of the abovementioned applications of isosorbideand other internal dehydration products of hydrogenated sugars, inparticular the other isohexides, it is generally required to apply apurification treatment to the compositions resulting directly from theactual dehydration step. This is in particular because any hydrogenatedsugar subjected to such a step (for example sorbitol) is likely, duringthe said step, to be converted to, apart from the desired dehydrationproduct (for example isosorbide), various coproducts such as:

[0020] isomers of the said desired product, for example isomers ofisosorbide such as isomannide and isoidide,

[0021] products which are less dehydrated than the desired product orthan its isomers, for example sorbitan, mannitan or iditan,

[0022] derivatives resulting from the oxidation or more generally fromthe degradation of the abovementioned products, it being possible forthese derivatives to include, for example when the desired product isisosorbide, coproducts of the type such as deoxymonoanhydrohexitols,monoanhydropentitols, monoanhydrotetritols, anhydrohexoses,hydroxymethylfurfural, or glycerin,

[0023] derivatives resulting from the polymerization of theabovementioned products, and/or

[0024] highly coloured species of a poorly defined nature.

[0025] It should be recalled that, in general, all or some of thesevarious categories of coproducts or impurities are generated to agreater or lesser degree during the actual step of dehydration of thehydrogenated sugar, this being independently of the conditions andprecautions used in practice during the said step, and for exampleindependently:

[0026] of the nature and of the form of presentation of the dehydrationacid catalyst used (inorganic acid, organic acid, cationic resin, andthe like), or

[0027] of the quantity of water or of organic solvent(s) in the initialreaction medium, or

[0028] of the purity of the hydrogenated sugar, for example sorbitol,composition used as raw material.

[0029] Various technologies have been recommended for the purposes ofobtaining compositions derived from the said dehydration step, forexample compositions of isohexide(s), which are improved in terms ofpurity, this being in a “direct” manner by adjusting the reactionconditions during the said step and/or in an “indirect” manner byapplying one or more purification treatments after the said step.

[0030] CA patent 1 178 288 recalls on its page 14, lines 3-8 that it isrecommended to carry out the actual dehydration reaction under an inertgaseous atmosphere in order to avoid oxidation reactions, in particularwhen relatively high temperatures and long reaction times are envisaged.

[0031] U.S. Pat. No. 4,861,513 describes a sorbitol dehydration reactioncarried out simultaneously in the presence of an inert gas (nitrogen)and a reducing agent (sodium hypophosphite) for the preparation ofparticular mixtures of polyols, which have a low content (10 to 26%) ofdianhydrosorbitol.

[0032] For its part, GB patent 613,444 describes the production, bydehydration in a water/xylene medium, of an isosorbide composition whichis then subjected to a treatment of distillation and then ofrecrystallization from an alcohol/ether mixture.

[0033] A purification treatment combining distillation andrecrystallization from a lower aliphatic alcohol (ethanol, methanol) hasalso been recently recommended in patent WO 00/14081. This documentmoreover indicates that, in the case where distillation is the onlypurification step envisaged, it is advantageous to carry out the saidstep in the presence of sodium borohydride.

[0034] The passage on page 11, lines 13-21 of the said patent describesthe distillation “in an inert atmosphere (argon)” of an isosorbidecomposition previously brought into contact with sodium borohydride(NaBH4) According to table 1 of this patent, it appears that thisdistillation makes it possible to increase the purity of the initialproduct (“C-ISOS”) by a value of 98.79 to 99.07%.

[0035] Other authors have also recommended that the distillation step becarried out in the presence of a boron-containing compound, inparticular of boric acid or of an anionic resin previously charged withborate ions, as described in U.S. Pat. No. 3,160,641.

[0036] Patents U.S. Pat. No. 4,408,061 and EP 323,994 envisage the useof particular dehydration catalysts (gaseous hydrogen halide and liquidhydrogen fluoride respectively), advantageously combined with carboxylicacids as cocatalysts followed by the distillation of the crudeisosorbide or isomannide compositions thus obtained.

[0037] U.S. Pat. No. 4,564,692 mentions, without giving any details,prepurification on “ion exchangers and/or activated charcoal” ofisosorbide or isomannide compositions followed, after concentration byevaporation and seeding of crystals of the desired isohexide, bycrystallization thereof from water.

[0038] EP patent 380,402 claims, for its part, the dehydration ofhydrogenated sugars in the presence of hydrogen under pressure and ofparticular catalysts based on a combination between copper and a noblemetal of Group VIII or gold. These conditions are presented as making itpossible to significantly reduce the formation of impurities of apolymeric nature during the actual dehydration step.

[0039] More recently, there has been described in EP patent 915,091 thepossibility of further advantageously reducing the genesis of suchundesirable polymers, this being by using acid-stable hydrogenationcatalysts during the dehydration step.

[0040] However, the abovementioned documents do not relate specificallyto the questions of stability over time of the purified compositionsthus obtained and which have to be marketed, in particular to theirstability over time under conventional conditions of storagetemperature, i.e. generally between 0 and 40° C.

[0041] This results from the fact that isosorbide is generallyconsidered, as underlined on page 600, point 4. of the abovementionedarticle by H. R. KRICHELDORF, as an aliphatic diol which is particularlychemically and thermally stable.

[0042] At the end, nevertheless, of an in depth study of thesequestions, the Applicant Company has first of all made the doubleobservation according to which:

[0043] 1) not only was the level of stability of a composition asenvisaged here, for example an isosorbide composition, not correlatedwith its level of purity,

[0044] 2) but further, the use of an agent such as gaseous nitrogen orsodium borohydride as described in the prior art, i.e. at the latest atthe time of the distillation step, did not make it possible tosignificantly improve this stability.

[0045] And it is while further pursuing these studies that the ApplicantCompany found that, surprisingly and unexpectedly, only the use a) ofspecific stabilizing agents, in this case in nongaseous form, and b) ata particular time of the method of preparation, in this case after theactual distillation step, made it possible to achieve this aim and inparticular to prepare isosorbide compositions whose behaviour duringstorage, at least at ambient or moderate temperature, was improved. Forthese studies, the Applicant Company developed a test for stabilityduring storage at 40° C. which will be described later and which makesit possible to more rapidly evaluate the stability of compositionswhich, in the industrial reality, are generally stored at lowertemperatures, i.e. at room temperature.

[0046] Accordingly, the present invention concerns a method forpreparing a composition of internal dehydration product of ahydrogenated sugar, the said method being characterized in that itcomprises:

[0047] a) a step of distilling a medium containing the said internaldehydration product in order to obtain a distillate enriched with thisproduct,

[0048] b) optionally, at least one subsequent step of purifying thedistillate thus obtained,

[0049] c) a subsequent step of bringing the distillate obtained duringstep a), and then optionally subjected to step b), into contact with anagent capable of improving the stability of the internal dehydrationproduct predominantly contained in the distillate, the said agent notbeing in gaseous form,

[0050] d) optionally, a subsequent step of shaping the resultingcomposition of internal dehydration product of a hydrogenated sugar.

[0051] The agent used during step c) subsequent to step a) ofdistillation properly speaking (hereinafter “improving agent”) may be ofa varied nature.

[0052] In accordance with the present invention, it cannot consist of anagent of a gaseous nature such as nitrogen gas, in any case not solelyof such an agent.

[0053] The Applicant Company indeed observed, as will be moreoverexemplified, that the fact that an isosorbide composition was storedunder an inert atmosphere such as nitrogen gas without introducingtherein an improving agent in accordance with the invention, did notmake it possible, in the end, to obtain an isosorbide composition whosestability over time was truly improved in relation to the same productstored under air.

[0054] According to a first variant of the invention, the improvingagent used in the abovementioned step c) is chosen from the groupcomprising reducing agents, antioxidants, oxygen scavengers, lightstabilizers, anti-acid agents, metal-deactivating agents and anymixtures of at least any two of these products.

[0055] All these agents may be of a natural or synthetic origin, of aninorganic or organic nature.

[0056] The expression “reducing agents” is understood to mean anycompound having electron donating properties.

[0057] These compounds may correspond to those described in the chapterentitled “Reduction” on pages 687 to 716, Volume A22 of the 5th editionof the book “Ullmann's Encyclopedia of Industrial Chemistry” (1993)VCHVerlagsgesellschaft mbH, Weinheim (Germany).

[0058] They may be in particular compounds based on boron or aluminiumsuch as the boron or aluminium hydrides described on pages 699-703 ofthe abovementioned chapter and in particular sodium borohydride (NaBH4)or lithium aluminium hydride (LiAlH4).

[0059] The Applicant Company has discovered, as will be moreoverexemplified, that in contrast to its use before step a) of distillation,the use of NaBH₄ in the abovementioned step c), i.e. after distillation,made it possible to obtain an isosorbide composition whose stability wassignificantly improved.

[0060] The reducing agent used in accordance with the invention may alsoconsist of a compound based on phosphorus such as a phosphine or aphosphite.

[0061] The improving agent may also be chosen, as indicated above, fromantioxidants. The expression “antioxidants” is understood to mean inparticular any compound directly or indirectly capable of limiting oreven preventing, regardless of its mode of action, the complex phenomenaof oxidation, including autooxidation, of organic substances of naturalor synthetic origin, of a monomeric or polymeric nature.

[0062] These compounds may correspond to those described in chapter 1entitled “Antioxidants” of the 5th edition of the book “PlasticsAdditives Handbook” (2001) Carl Hanser Verlag, Munich (Germany) or toany mixture of at least any two of these compounds.

[0063] Such compounds may act according to at least one of themechanisms described on pages 10 to 19 of the said chapter and may havea chemical structure in accordance with one of those presented in thepassage corresponding to pages 97 to 139 of the said chapter.

[0064] They may be in particular compounds based on nitrogen, inparticular aromatic or nonaromatic amines, further containing, or not,at least one alcohol functional group.

[0065] They may be in particular hydroxylamine, morpholine, derivativesthereof and/or one of the compounds described under the codes “AO-7”,“AO-15”, “AO-16”, “AO-26” to “AO-28” and “AO-35” to “AO-41” of theabovementioned passage.

[0066] The antioxidant which may be used as improving agent for thepurposes of the invention may also consist of a nitrogenous ornon-nitrogenous aromatic compound containing or not at least one alcoholfunctional group, and may consist, for example, of phenolic compoundssuch as hydroquinone, phenol, tocopherols and the respective derivativesthereof and/or of one of the compounds described in the abovementionedpassage under the codes “AO-1” to “AO-42”.

[0067] They may be in particular, 2,6-di-tert-butyl-4-methylphenol(BHT), hydroquinone or mixtures thereof.

[0068] The expression “tocopherols and derivatives” is understood tomean in particular all the products described in patent WO 99/33776 inthe name of the Applicant, in particular in the passage on page 11, line14 to page 12, line 11 of the said patent. They may advantageously be acompound wholly or partly consisting of α-tocopherol and in particularof vitamin E.

[0069] Furthermore, the improving agent used in accordance with theinvention may consist of an antioxidant compound based on phosphorus oron sulphur such as those described in the abovementioned chapter of“Plastics Additives Handbook”, for example under the codes “PS-1” to“PS-12” and “TS-1” to “TS-4”.

[0070] It may in particular be chosen from the group comprisingphosphites, phosphonites, sulphites, the salts of esters ofthiodipropionic acid and mixtures thereof.

[0071] The improving agent for the purposes of the present invention mayalso consist, as indicated above, of a light stabilizer. This definitionincludes the compounds described on page 141 to 425 of “PlasticsAdditives Handbook” cited above, in particular the compounds based, ornot, on nitrogen or sulphur, which are aromatic or not, containing ornot at least one alcohol functional group, which are mentioned therein,in particular under the codes “UVA-1” to “UVA-27” and HA(L)S-1” to“HA(L)S-52”.

[0072] The improving agent may also be chosen from anti-acid agents,this definition including the compounds described in the chapterentitled “Acid Scavengers” on pages 485 to 510 of the book “PlasticsAdditives Handbook” cited above.

[0073] This definition also includes alkaline agents, in particularthose which are capable of being used as “buffers” in neutral oralkaline media and in particular in media having a pH of the order ofabout 7 to 9.

[0074] The alkaline agents may in particular consist of alkali metal, inparticular sodium or potassium, hydroxides, carbonates, borates orphosphates.

[0075] They may, by way of examples, be chosen from the group comprisingsodium hydroxide, potassium hydroxide, sodium carbonate, potassiumcarbonate, sodium metaborate, disodium phosphate and any mixtures ofthese products.

[0076] Finally, the said improving agent may advantageously be chosenfrom metal-deactivating agents, this definition including the compoundstermed “Metal Deactivators” as described on pages 18 and 113 of the saidbook but also the compounds described in the chapter entitled “CHELATINGAGENTS” on pages 764 to 795, Volume 5 of the 4th edition of the book“KIRK-OTHMER ENCYCLOPEDIA OF CHEMICAL TECHNOLOGY” (1993) John Wiley &Sons, Inc.

[0077] These metal-deactivating agents may consist in particular ofmetal-complexing or -chelating agents of natural origin, in particularcontaining at least one alcohol functional group, and in particularobtained from starchy substances such as gluconates, glucoheptonates,phytates, lactates or citrates.

[0078] The Applicant Company has in particular found that the said agentcould advantageously be capable of complexing or chelating metals suchas iron, copper, cobalt, manganese or nickel. In industrial practice, inparticular during manufacturing, forming and storage operations, it isdifficult to avoid all metal contamination in such compositions.

[0079] According to another variant of the invention, in particular whenthe composition of the internal dehydration product should be subjectedto severe regulatory constraints, the improving agent may beadvantageously chosen from the products authorized as food additives, inparticular those termed “antioxidants”, “acidity regulators” or“sequestrants” within the meaning of the European regulations, inparticular of Directive 95/2/EC of the European Parliament and of theCouncil of Feb. 20, 1995 and of subsequent amendments thereof.

[0080] The improving agent may then in particular be chosen from thegroup comprising ascorbic acid (vitamin C), erythorbic acid, lacticacid, citric acid, gallic acid, tocopherols, derivatives (in particularsalts) of all these products, BHT, butylated hydroxyanisole (BHA) andany mixtures of these products.

[0081] The improving agent may be used in step c) in very smallproportions, namely of the order of 0.0001% (1 ppm) to 2%, thesepercentages being expressed by dry weight of improving agent relative tothe dry weight of the internal dehydration product of a hydrogenatedsugar then predominantly present in the distillate, for exampleisosorbide, then present in this medium.

[0082] According to a first variant of the method according to theinvention, the improving agent is used in step c) of the said method inan amount of 0.001 to 2%, preferably 0.002 to 1.5% and still morepreferably 0.003 to 1.5%.

[0083] The Applicant Company has found in particular that this amount ofintroduction could advantageously be between 0.005 and 1%, for examplewhen the improving agent consisted of NaBH₄ or an antioxidant such asBHT, morpholine, hydroxylamine, vitamin C, hydroquinone, sodiumerythorbate or compounds described under the codes “AO-18” or “PS-2” inthe abovementioned literature.

[0084] According to another variant of the method according to theinvention, the improving agent is used in step c) of the said method inan amount of 0.0001 (1 ppm) to 0.5%, preferably 0.0003 (3 ppm) to 0.3%.

[0085] The Applicant Company has in particular found that this rate ofintroduction could advantageously be between 0.0003 (3 ppm) and 0.1%when the improving agent consisted of a reducing agent such as NaBH₄ orof an anti-acid agent such as an alkaline agent like sodium metaborateor disodium phosphate.

[0086] Such low levels of improving agent, for example of 0.0003% (3ppm) to 0.01% (100 ppm) of NaBH₄ or of another sodium salt, may inparticular be advantageously used for the purpose of satisfying, inaddition, technical and/or regulatory constraints which may existdepending on the particular application for which the stabilizedcomposition in accordance with the invention is intended.

[0087] In the context of the method according to the invention, itshould be specified that the medium subjected to step a) of distillationmay be of a highly varied nature, including in terms of dry mattercontent, of temperature and/or of purity in relation to the desireddehydration product.

[0088] It may be, according to a first variant, an isosorbidecomposition consisting of the medium directly derived from the actualdehydration reaction and having a purity in relation to the desiredproduct, for example in relation to isosorbide, of the order of 50 to80%.

[0089] According to another possibility, the said composition may,because in particular it already results from one or more previouspurification operations, in particular by distillation and/orcrystallization, have a purity in relation to the desired product, forexample in relation to isosorbide, of greater than 80%.

[0090] Advantageously, step a) of distillation is followed by a step b)of purification of the resulting distillate.

[0091] According to a first variant, step b) consists of a purificationstep according to which the distillate, generally dissolved in solution,is treated with at least one purification means chosen fromdecolorization means and ion-exchange means.

[0092] The expression “decolorization means” is understood to mean inparticular activated charcoal in granular or pulverulent form andadsorption resins.

[0093] By way of example, it is possible to use, alone or incombination, granular activated charcoal such as the product “CECA DC50”, pulverulent activated charcoal such as the product “NORIT SX +”and/or a resin such as those called “DUOLITE XAD 761”, “MACRONET MN-600”or “MACRONET MN-400”.

[0094] The expression “ion-exchange means” is understood to mean inparticular weak or strong anionic resins, and weak or strong cationicresins.

[0095] By way of example, it is possible to use, alone or incombination, a strong anionic resin such as the resin “AMBERLITE IRA910” or a strong cationic resin such as the resin “PUROLITE C 150 S”.

[0096] The ion-exchange means may advantageously comprise at least oneanionic resin and at least one cationic resin. Preferably, this means iscomposed of a mixed bed of anionic and cationic resin(s) or a successionof cationic and then anionic resin(s) or a succession of anionic andthen cationic resin(s).

[0097] Preferably, during step b) of the method in accordance with theinvention, the distillate obtained during step a) is treated, in anyorder, with at least one activated charcoal and with at least one ionicor nonionic resin.

[0098] Very advantageously, the said distillate is first treated withactivated charcoal and then with at least one resin and then again withactivated charcoal.

[0099] According to another variant of the method according to theinvention, the Applicant Company has found that it was particularlyadvantageous for the composition subjected to step b) of purification toalready have certain characteristics in terms of maximum content ofparticular impurities, for example of formic acid and of species of the“monoanhydrohexose” type.

[0100] It also found that such a content could in particular be ensuredby directly subjecting the distillate obtained during step a) to thesaid step b) of purification.

[0101] The method according to the invention may therefore becharacterized in that the distillate subjected to the said step b) has aformic acid content of less than 0.002% (20 ppm) and a content ofmonoanhydrohexoses of less than 0.02% (200 ppm), these percentages beingexpressed by dry weight relative to the dry weight of the internaldehydration product of a hydrogenated sugar then predominantly presentin the said distillate, for example to the dry weight of isosorbidepresent in the said distillate.

[0102] The distillate may in particular have a formic acid content ofless than 0.0005% (5 ppm) and a content of monoanhydrohexoses of lessthan 0.005% (50 ppm). According to another variant and advantageously,the improving agent used according to the invention is used directlyafter step b) of purification and in particular, as will be furtherexemplified, introduced directly into the purified aqueous solution ofinternal dehydration product derived from step b), which solutiongenerally has a temperature at most equal to 60° C.

[0103] Regardless of the mode of operation of the method which is thesubject of the invention, the Applicant Company also found that it couldbe advantageous for all or part of step c), during which the improvingagent is present, to be carried out in a medium which is liquid andwhose temperature is at least equal to the softening or meltingtemperature of the desired internal dehydration product (for exampleisosorbide) but less than about 140° C.

[0104] This temperature may, in particular in the case of isosorbide, bebetween 60 and 135° C.

[0105] These conditions improve the homogeneous distribution of theimproving agent in the resulting composition, in particular if thelatter has to be cooled and then shaped in accordance with the optionalstep d).

[0106] In this regard, the Applicant Company thinks that it may beadvantageous for the said improving agent to have minimal solubility inwater and/or in the desired internal dehydration product.

[0107] In particular, the present invention may also be characterized inthat the said improving agent has a solubility, in water at 20° C., atleast equal to 0.01%, preferably at least equal to 0.1%.

[0108] After step c) and as indicated above, the composition of internaldehydration product of a hydrogenated sugar obtained according to theinvention may be shaped during a subsequent step d).

[0109] This step may consist of an operation of pelleting or scaling ofthe crystallized mass or “massed product” resulting from cooling, inparticular by contact with a cold surface, of the composition derivedfrom step c).

[0110] Step d) of shaping may, if desired, be followed by a step ofgrinding and/or sieving, this being before any step of storing and/orpackaging in bags the composition thus obtained.

[0111] According to another variant, the composition of internaldehydration product of a hydrogenated sugar obtained according to theinvention may, after step c), be stored as it is, in particular in theliquid or paste state, with no subsequent specific shaping step.

[0112] The composition resulting from the method according to theinvention may moreover have been subjected, at any moment, to aconcentration step, in particular a step of evaporation under vacuum,the said step being performed under the mildest possible conditions, inparticular in terms of duration and temperature.

[0113] According to a first variant, the said concentration step iscarried out, completely or partly, simultaneously with step c) inaccordance with the invention.

[0114] According to another variant, the said concentration step iscarried out, completely or partly, prior to step c) in accordance withthe invention, preferably immediately before the said step c).

[0115] In any case, it is advantageous to carry out the saidconcentration step directly after step b) of purification, as soon asthis step b) has been carried out.

[0116] Accordingly, regardless of the moment when one concentration stepat least has been carried out in the context of the method in accordancewith the invention, including therefore prior to step c), the saidmethod makes it possible to prepare a stable liquid composition ofinternal dehydration product of a hydrogenated sugar, in particular astable liquid isosorbide composition, whose dry matter (“DM”) content ishigh, i.e. between 50 and 90%, in particular between 75 and 88%.

[0117] This DM may in particular be of the order of about 85%.

[0118] All the steps of the method according to the invention,obligatory or optional, which have just been described may in addition,if desired, be carried out under an inert atmosphere, including step c)characteristic of the present invention and/or any subsequent step, inparticular of shaping, of storing or of packaging in bags.

[0119] Accordingly, a new means is available which is capable ofproviding a composition of an internal dehydrogenation product of ahydrogenated sugar, for example an isosorbide composition, whosestability is improved, such a stability being required regardless of theuses for which the said composition is intended and regardless moreoverof the purity of the said composition.

[0120] It is remarkable to underline that the method according to theinvention makes it possible to obtain in particular a composition of thetype in question which, although having a purity which is indeed highbut nonoptimum, is found to be stable. The expression “stablecomposition” for the purposes of the present invention is understood tomean a composition which, when stored in a noninert atmosphere for aperiod of at least one month and at a temperature of 40° C., has both aformic acid content of less than 0.0005% (5 ppm) and an overall contentof monoanhydrohexoses of less than 0.005% (50 ppm), these percentagesbeing expressed by dry weight relative to the dry weight of the saidcomposition. This stability may obviously be very significantly greaterthan 1 month and may be up to at least two months, preferably at least 6months and still more preferably at least one year; which means that,under normal storage conditions, i.e. at room temperature, thecompositions according to the invention can be stored for significantlylonger periods than those mentioned above.

[0121] A novel product is henceforth available, inter alia, whichconsists of a composition of isosorbide or another internal dehydrationproduct of a hydrogenated sugar, which is stable according to thedefinition which has just been given and which simultaneously has apurity of less than 99.8%, which is in particular between about 98.0 and99.7%.

[0122] Remarkably, the said composition has a stability of at least twomonths, preferably of at least six months, and still more preferably ofat least one year.

[0123] The Applicant Company has in particular found that a compositionin accordance with the invention was most particularly capable of havingsuch a stability so long as it had a pH greater than 5, preferablygreater than 6 and in particular of between about 6.5 and 9.5,regardless of its form of presentation and its dry matter content.

[0124] In a particularly advantageous manner, the said composition has apH of between about 7 and 9, the measurement of the pH being carried outafter adjusting the dry matter content of the said composition to avalue of 40%, this being by any dilution or concentration meansavailable to persons skilled in the art.

[0125] The Applicant Company in fact considers as novel compositions asenvisaged here, in particular isosorbide compositions havingsimultaneously such a stability of at least two months and such a pH,measured as described above, in the abovementioned ranges.

[0126] The novel composition according to the invention may also becharacterized in that it contains, in particular, from 0.0001 to 2% ofan improving agent as described above, these percentages being expressedby dry weight of improving agent relative to the dry weight of theinternal dehydration product of a hydrogenated sugar, for exampleisosorbide, predominantly present in the composition.

[0127] According to a first variant, the said composition contains from0.001 to 2%, preferably from 0.002 to 1.5% and still more preferablyfrom 0.003 to 1.5% of an improving agent, it being possible for thelatter in particular to consist of NaBH₄ or of an antioxidant.

[0128] In the case of the use of an improving agent consisting of aboron-containing compound such as NaBH₄ containing about 28.6% boron,the said composition can therefore contain from about 0.00029 to 0.572%of boron. These percentages of boron will be higher and up to about 1%if a compound such as Li BH₄, which is more rich in boron (about 49.7%),is used in place of NaBH₄.

[0129] If account is taken of other elements such as nitrogen, sodium,potassium, phosphorus or sulphur, which may be contained to a greater orlesser degree in the improving agents used according to the invention,their presence in the resulting composition can also be highly variablebut in any case will be generally at most equal to about 1% as well.

[0130] This will be necessarily the case when, according to a secondvariant, the composition according to the invention will contain evenlower levels, i.e. from 0.0001 to 0.5%, preferably from 0.0003 to 0.3%,and in particular from 0.0003 to 0.1%, of an improving agent, it beingpossible for the latter in particular to consist of a reducing agent(including NaBH₄) or of an anti-acid agent (including an alkalineagent).

[0131] The Applicant Company in fact considers as novel compositions asenvisaged here, in particular isosorbide compositions which contain from0.0001 to 1% of an element chosen from the group comprising boron,sodium, potassium, phosphorus, sulphur or nitrogen, these percentagesbeing expressed by dry weight/dry weight in the same manner as thatdescribed above for the improving agents as such.

[0132] These compositions, in particular of isosorbide, may inparticular contain from 0.0001 to 0.01% of one of the abovementionedelements.

[0133] Such compositions may in particular be used for the preparationof polymeric or nonpolymeric, biodegradable or nonbiodegradable productsor mixtures intended for the chemical, pharmaceutical, cosmetic or foodindustries.

[0134] The present invention will be described in even greater detailwith the aid of the following examples which are not at all limiting.

EXAMPLE 1

[0135] 1 kg of a sorbitol solution containing 70% DM, marketed by theapplicant under the name “NEOSORB® 70/02” and 7 g of concentratedsulphuric acid are introduced into a jacketed stirred reactor. Themixture obtained is heated under vacuum (pressure of about 100 mbar) for5 hours so as to remove the water contained in the initial reactionmedium and that obtained from the sorbitol dehydration reaction.

[0136] The crude reaction product is then cooled to around 100° C. andthen neutralized with 11.4 g of a 50% sodium hydroxide solution. Theisosorbide composition thus neutralized is then distilled under vacuum(pressure of less than 50 mbar).

[0137] The slightly coloured (light yellow colour) crude isosorbidedistillate is then dissolved in distilled water so as to obtain asolution containing 40% DM.

[0138] This solution is then percolated on a “CECA DC 50” granularactivated charcoal column at a rate of 0.5 BV/h (Bed Volume/hour). Thedecolorized isosorbide composition thus obtained is then passed, at arate of 2 BV/h, successively over a column of “PUROLITE C 150 S” strongcationic resin and then a column of “AMBERLITE IRA 910” strong anionicresin.

[0139] The isosorbide solution is then directly concentrated undervacuum. The molten mass obtained crystallizes on cooling in the form ofa “massed product” consisting of large crystals which are then ground inorder to obtain a white powder having a moisture content of 0.3%.

[0140] Its respective contents of formic acid and monoanhydrohexoses areless than 0.0005% (5 ppm), each expressed by dry weight relative to thedry weight of the said composition.

[0141] 20 g of this massed product of isosorbide are directly introducedinto a glass container having a capacity of 50 ml which, after havingbeen hermetically closed, is placed in an oven maintained at 40° C.

[0142] After 1 month of storage under these conditions, the isosorbidecomposition has a formic acid content of 1000 ppm and a content ofmonoanhydrohexoses of about 7000 ppm.

[0143] The “massed product” of isosorbide thus tested cannot thereforebe considered as being stable, for the purposes of the presentinvention.

EXAMPLE 2

[0144] In this example, in accordance with the invention, there isrecovered a fraction of the isosorbide solution directly derived, afterdistillation, from the treatment consisting of passing over activatedcharcoal and then resins as described in EXAMPLE 1, a solution whose drymatter content and isosorbide purity were measured.

[0145] As soon as it is recovered, there is introduced into the saidfraction a quantity of NaBH₄ corresponding to 0.005% (50 ppm) by weightof the weight of isosorbide contained in the said fraction (dryweight/dry weight) and then the concentration step is directly carriedout, this being under the same conditions as those described in EXAMPLE1.

[0146] The massed product obtained directly after cooling hascharacteristics of purity (about 99.1%) and of content of formic acidand of monoanhydrohexoses which are logically of the same order as thoseof the massed product obtained during EXAMPLE 1.

[0147] However, after 1 month of storage under the same conditions asthose described in EXAMPLE 1, the isosorbide composition thus adjuvantedwith NaBH4 after distillation still has respective contents of formicacid and monoanhydrohexoses of less than 5 ppm.

[0148] This composition can therefore be considered as being stable forthe purposes of the present invention.

[0149] Additional measurements have in fact shown that, after more than6 months of storage under the same conditions, this same compositionstill had a formic acid content of less than 5 ppm and a content ofmonoanhydrohexoses significantly less than 50 ppm. Accordingly, thiscomposition has a stability of at least six months for the purposes ofthe invention.

EXAMPLE 3

[0150] In this example, not in accordance with the invention, there isrecovered a fraction of the crude reaction product directly derived fromthe neutralization step as described in EXAMPLE 1, a neutralized crudereaction product whose dry matter content and isosorbide purity weremeasured.

[0151] As soon as it is recovered, there is introduced into the saidfraction a quantity of NaBH₄ corresponding to 0.02% (200 ppm) of theisosorbide contained in the said fraction (dry weight/dry weight) andthen the steps of distillation under vacuum, of purification onactivated charcoal and then resins, of concentration and of cooling asdescribed in EXAMPLE 1 are directly carried out.

[0152] The massed product obtained directly after cooling hascharacteristics of purity and of content of formic acid and ofmonoanhydrohexoses which are of the same order as those of the massedproduct obtained during EXAMPLE 2.

[0153] However, after 1 month of storage under the same conditions asthose described in EXAMPLE 1, the isosorbide composition thus obtainedhas a formic acid content of 1200 ppm and a content ofmonoanhydrohexoses content of about 5000 ppm.

[0154] This example shows that the use of a product such as NaBH₄ beforethe actual distillation step does not make it possible, in the end, toconfer on the resulting isosorbide composition a stability character forthe purposes of the present invention.

EXAMPLE 4

[0155] In this example, not in accordance with the invention, a massedproduct is obtained under the same conditions as those of EXAMPLE 1except that all the steps subsequent to step b) of purification arecarried out in an inert atmosphere, under nitrogen.

[0156] The massed product has characteristics of formic acid andmonoanhydrohexose purity and content which are of the same order asthose of the massed product obtained in EXAMPLE 1.

[0157] However, after 1 month of storage under the same conditions asthose of EXAMPLE 1, the isosorbide composition thus obtained has aformic acid content of 700 ppm and a content of monoanhydrohexoses ofabout 6000 ppm.

[0158] This example shows that the sole use of nitrogen gas, even afterthe distillation step, does not make it possible, in the end, to conferon the resulting isosorbide composition a stability character for thepurposes of the present invention.

EXAMPLE 5

[0159] In this example, in accordance with the invention, the procedureis carried out as described in EXAMPLE 2, except that:

[0160] 1) after its passage over activated charcoal and then resins, thedistillate is treated with 5% (dry weight/dry weight) of powderedactivated charcoal “NORIT SX +” at 20° C. for 1 hour, and

[0161] 2) 50 ppm of respectively NaBH₄, morpholine, BHT or vitamin C aredirectly introduced into the distillate thus treated, beforeconcentration.

[0162] Each of the four massed products obtained directly after theconcentration and cooling steps was stored under the same conditions asthose described in EXAMPLE 1.

[0163] After 1 or 2 months of storage at 40° C., none of these fourproducts saw its formic acid content reach the value of 5 ppm or itscontent of monoanhydrohexoses reach the value of 50 ppm.

[0164] Remarkably, tests carried out for 6 months and more under thesame conditions on the massed products derived from the distillatestreated with NaBH₄ or morpholine moreover showed that this stabilitycould be maintained at least for this duration.

[0165] Isosorbide compositions are thus available which have a stabilityof at least two months, in particular of at least six months.

EXAMPLE 6

[0166] A decolorized and purified isosorbide solution is prepared asdescribed in EXAMPLE 1.

[0167] This solution is, after passing over a strong cationic resin andthen a strong anionic resin, directly concentrated under vacuum, to adry matter content of about 85%.

[0168] The pH of this isosorbide composition, measured after adjustingits dry matter content to a value of 40% by dilution in distilled water,is of the order of 5.0.

[0169] It was then observed, during a storage test performed asdescribed above at 40° C., that such a composition could not beconsidered as being stable for the purposes of the present invention.

[0170] Isosorbide compositions in accordance with the invention areprepared by introducing, into an isosorbide solution which has beendecolorized, purified and concentrated to 85% as described above andimmediately after the concentration step, small quantities of improvingagent consisting respectively of:

[0171] 0.0002% (2 ppm) of NaBH₄, or

[0172] 0.0010% (10 ppm) of NaBH₄, or

[0173] 0.0005% (5 ppm) of NaOH, or

[0174] 0.0012% (12 ppm) of NaBO₂, or

[0175] 0.0015% (15 ppm) of Na₂HPO₄.

[0176] The pH of the compositions thus obtained varies from about 6.6 to8.6.

[0177] The Applicant Company then observed, during storage testsperformed at 40° C. as described above, that all these compositionscould not only be considered as being stable for the purposes of thepresent invention, but further that this stability was of at least twomonths.

[0178] It has already been verified in some of the said compositionsthat this stability was of at least three months, or even six months orone year.

[0179] Accordingly, it is observed that the use of very small quantitiesof improving agents, i.e. at most equal to 0.1% (dry weight/dry weight),in particular between 0.0001% (1 ppm) and 0.01% (100 ppm) and includingof less than 0.005% (50 ppm), made it possible to have a simple andinexpensive means of stabilizing compositions of the type in question,this means being moreover generally capable of satisfying the technicaland/or regulatory constraints to which the said compositions may besubjected.

[0180] Without wishing to be bound by any theory, the Applicant Companyconsiders that the effect caused by such a use on the pH of the saidcompositions may, directly or indirectly, play, at least partially, arôle in the increase in the stability of the said compositions, in anycase in their specific stability at ambient or moderate temperature (40°C.).

1. Method for preparing a composition of internal dehydration product ofa hydrogenated sugar, comprising: a) a step of distilling a mediumcontaining the said internal dehydration product in order to obtain adistillate enriched in this product, b) optionally, at least onesubsequent step of purifying the distillate thus obtained, c) asubsequent step of bringing the distillate obtained during step a), andthen optionally subjected to step b), into contact with an agent capableof improving the stability of the internal dehydration productpredominantly contained in the distillate, the said agent not being ingaseous form, d) optionally, a subsequent step of shaping the resultingcomposition of internal dehydration product of a hydrogenated sugar. 2.Method according to claim 1, wherein the agent used in step c) isselected from the group consisting of reducing agents, antioxidants,oxygen scavengers, light stabilizers, anti-acid agents,metal-deactivating agents and any mixtures of at least any two of theseproducts.
 3. Method according to claim 1, wherein the agent used in stepc) is selected from the group consisting of compounds based on boron,compounds based on sodium, compounds based on potassium, compounds basedon phosphorus, compounds based on nitrogen, compounds based on sulphur,aromatic compounds, compounds containing at least one alcohol functionalgroup and any mixtures of at least any two of these products.
 4. Methodaccording to claim 1, wherein the agent used in step c) is used in anamount of 0.0001 to 2%, these percentages being expressed by dry weightof the said agent relative to the dry weight of the internal dehydrationproduct of a hydrogenated sugar predominantly present in the distillate.5. Method according to claim 4, wherein the agent is used in an amountof 0.001 to 2%, preferably 0.002 to 1.5% and still more preferably 0.003to 1.5%.
 6. Method according to claim 5, wherein the agent is used in anamount of 0.005 to 1%.
 7. Method according to claim 6, wherein the agentconsists of sodium borohydride (NaBH₄) or an antioxidant.
 8. Methodaccording to claim 4, wherein the agent is used in an amount of 0.0001to 0.5%, preferably 0.0003 to 0.3%.
 9. Method according to claim 8,wherein the agent is used in an amount of 0.0003 to 0.1%.
 10. Methodaccording to claim 9, wherein the agent is used in an amount of 0.0003to 0.01%.
 11. Method according to claim 9, wherein the agent consists ofa reducing agent or of an anti-acid agent, the anti-acid agent beingpreferably selected from alkaline agents.
 12. Method according to claim11, wherein the agent is a sodium salt.
 13. Method according to claim 1,wherein the agent used in step c) has a solubility in water at 20° C. atleast equal to 0.01%, preferably at least equal to 0.1%.
 14. Methodaccording to claim 1, wherein step a) of distillation is followed by astep b) of purification, preferably a step b) of purification duringwhich the distillate is treated, in any order, with at least oneactivated charcoal and with at least one ionic or nonionic resin. 15.Method according to claim 1, comprising at least one concentration stepcarried out, completely or partly, prior to or simultaneously with stepc).
 16. Composition containing at least one internal dehydration productof a hydrogenated sugar, containing from 0.0001 to 2% of an agentselected from the group consisting of reducing agents, anti-oxidants,oxygen scavengers, light stabilizers, anti-acid agents,metal-deactivating agents and any mixtures of at least any two of theseproducts, these percentages being expressed by dry weight of the saidagent relative to the dry weight of the internal dehydration product ofa hydrogenated sugar predominantly present in the said composition. 17.Composition according to claim 16, containing from 0.005 to 1% of anagent consisting of sodium borohydride or of an antioxidant. 18.Composition according to claim 16, containing from 0.0003 to 0.1% of anagent consisting of a reducing agent or of an anti-acid agent, theanti-acid agent being preferably selected from alkaline agents. 19.Composition containing at least one internal dehydration product of ahydrogenated sugar, containing from 0.0001 to 1% of an element selectedfrom the group consisting of boron, sodium, potassium, phosphorus,sulphur or nitrogen, these percentages being expressed by dry weight ofthe said element relative to the dry weight of the internal dehydrationproduct of a hydrogenated sugar predominantly present in the saidcomposition.
 20. Composition according to claim 19, containing from0.0001 to 0.01% of an element selected from the group consisting ofboron, sodium, potassium, phosphorus, sulphur or nitrogen. 21.Composition containing at least one internal dehydration product of ahydrogenated sugar, being stable and having a purity of less than 99.8%,in particular a purity of between about 98.0 and 99.7%.
 22. Compositionaccording to claim 16 or claim 19, having a formic acid content of lessthan 0.0005% and a content of monoanhydrohexoses of less than 0.005%,these percentages being expressed by dry weight relative to the dryweight of the internal dehydration product of a hydrogenated sugarpredominantly present in the said composition.
 23. Composition accordingto claim 16 or claim 19, being an isosorbide composition. 24.Composition according to claims 16 or claim 19, having a stability of atleast two months, preferably of at least six months, and still morepreferably of at least one year.
 25. Composition according to claim 16or claim 19, having a pH greater than 5, preferably greater than 6 andstill more preferably of between about 6.5 and 9.5.
 26. Compositionaccording to claim 25, having a pH of between about 7 and
 9. 27.Composition according to claim 16 or claim 19, having a dry mattercontent of between 50 and 90%, preferably between 75 and 88%. 28.Polymeric or nonpolymeric, biodegradable or nonbiodegradable productsand mixtures intended in particular for the chemical, pharmaceutical,cosmetic or food industries, containing a composition according to claim1.